Studies of normal and pathological human cell physiology require appropriate cell culture systems, since in vivo experiments are not possible. The mammary gland provides an excellent source of human cells for culture, since abundant amounts of tissue are available from several commonly performed surgical procedures such as reduction mammoplasties, biopsies, gynecomastias, and mastectomies. In particular, mammary gland epithelial cells in culture can serve as valuable substrates for studies on carcinogenesis, differentiation, and basic cellular and molecular mechanisms. In vivo, the breast glandular epithelial cells are the cell type responsible for expression of the differentiated functions associated with synthesis of milk products; this behavior is under specific hormonal control. The breast epithelial cells are also the source of the second most common cancer in this country.
Eighty-five to ninety per cent of human cancers originate in epithelial cells. However, while transformation of cultured human fibroblastic and stromal cells by chemical carcinogens and radiation has been done, transformation in vitro of human epithelial cells has proved more difficult. Although epithelial cell cultures derived from numerous organs of rodent model systems have been neoplastically transformed by chemical carcinogens, little work has been done regarding carcinogen-induced transformation of human epithelial organ or cell cultures. Results obtained with rodents are not necessarily applicable to humans, and it is thus preferable to conduct experimentation with human cells directly. At present, however, there are no known continuous cell lines that have been verified as human mammary epithelium in origin are not virus transformed and which are useful for studying the effects of toxins, carcinogens and mutagens.
It is also preferable to conduct experimentation with continuous rather than with normal cell lines which have a finite life span, as work with the continuous cell lines is substantially more convenient. Furthermore, since carcinogenic events are most likely to occur during cell replication, and actively dividing cell culture system is strongly preferred. Previously, continuous cell lines were obtainable from two sources: from tumor cells, which can spontaneously transform to continuous at a low frequency, and in some cases, from normal cells which have been infected with a tumor virus or oncogenic material. These cell lines generally have an unstable chromosome complement, however, and thus are not particularly useful for studying carcinogenesis or mutagenesis.
There is thus a need in the art for a substantially genetically stable continuous human cell line useful in the study of the effects of chemicals and drugs considered to be potential toxins, carcinogens or mutagens. The present invention addresses this need and others by providing such a cell line derived from normal human mammary epithelial cells.